Fmoc-Val-Ala-OH

1115-74-8

28920-43-6

150114-97-9

The general procedure for the synthesis of N-[Fmoc]-L-valyl-L-alanine from the compound (CAS:1115-74-8) and 9-fluorenylmethyl chloroformate is as follows: (a) (R)-2-((R)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-methylbutanoylpropionic acid (20a, 350 mg, 1.86 mmol) and Na2CO3 (493 mg, 4.65 mmol) were dissolved in distilled water (15 mL) and the mixture was cooled to 0 °C. Dioxane (15 mL) was then added (some precipitation appeared). A solution of Fmoc-Cl (504 mg, 1.95 mmol) in dioxane (15 mL) was added dropwise with vigorous stirring over 10 min. The resulting mixture was stirred at 0°C for 2 hours. After removing the ice bath, stirring was continued for 16 hours. The solvent was removed by rotary evaporation under reduced pressure and the residue was dissolved in water (150 mL). The pH was adjusted from 9 to 2 with aqueous 1N HCl. The aqueous layer was subsequently extracted with EtOAc (3 x 100 mL). The organic layers were combined, washed with brine (100 mL), dried with MgSO4, filtered and the volatiles were removed by rotary evaporation under reduced pressure to give pure HO-Ala-Val-Fmoc (20b, 746 mg, 97% yield). LC/MS analysis: 2.85 min (ES+) m/z (relative intensity) 410.60. 1H-NMR (400 MHz, CDCl3) δ 7.79 (d, J = 7.77 Hz, 2H), 7.60 (d, J = 7.77 Hz, 2H), 7.43 (d, J = 7.5 Hz, 2H), 7.34 (d, J = 7.5 Hz, 2H), 6.30 (bs, 1H), 5.30 (bs, 1H), 4.71- 7.56 (m, 1H), 4.54-4.36 (m, 2H), 4.08-3.91 (m, 1H), 2.21-2.07 (m, 1H), 1.50 (d, J = 1AHz, 3H), 1.06-0.90 (m, 6H).